Controlled Study of Rigosertib Versus Physician's Choice of Treatment in MDS Patients After Failure of an HMA

Official Title

A Phase III, International, Randomized, Controlled Study of Rigosertib Versus Physician's Choice of Treatment in Patients With Myelodysplastic Syndrome After Failure of a Hypomethylating Agent

Summary:

The study's primary objective [in a population of patients with MDS after failure of
treatment with azacitidine (AZA) or decitabine (DAC)], is to compare the overall survival
(OS) of patients in the rigosertib group vs the Physician's Choice group, in all patients and
in a subgroup of patients with IPSS-R very high risk.

Trial Description

Primary Outcome:

Overall survival of all randomized patients and overall survival of patients scored as IPSS-R very high risk.

This is a Phase III, open-label, randomized, controlled, international study. Approximately
360 patients < 82 years of age with MDS classified as RAEB-1, RAEB-2, or RAEB-t who received
AZA or DAC for ≤ 9 months and/or ≤ 9 cycles over 12 months and had their last dose of AZA or
DAC within 6 months prior to screening will be stratified by:

Very high risk (VHR) vs non-VHR per IPSS-R, and

Geographic region (North America vs Europe vs Asia; because approved products and
standard of care may vary by region), and randomly assigned in a 2:1 ratio to one of the
following 2 treatment groups:

Rigosertib 1800 mg/24 hr administered as a 72 hr CIV infusion on Days 1, 2, and 3 of a 2
week cycle for the first 8 cycles, and on Days 1, 2, and 3 of a 4-week cycle thereafter
(N = approximately 240 patients);

Physician's Choice of alternative treatment, which may include any approved or
standard-of-care therapy that the patient has not shown to be hypersensitive to, based
on frequently used treatment for MDS, as per institutional guidelines, after receipt of
HMAs (N = approximately 120 patients). The drugs used in the Physician's Choice arm
should be used according to the recommendations, if clinically appropriate, provided in
the corresponding Summary of Product Characteristics (SmPC) and Prescribing Information
of these drugs. Experimental therapies are not allowed on the PC arm.
Patients will be treated until 2006 IWG progression criteria are met (ie, 50% increase of BM
blasts or worsening of cytopenias) or until an unacceptable toxicity or intolerance.
For all randomized patients who discontinue study treatment, subsequent therapies with their
start and end dates, as well as survival time after treatment discontinuation, will be
documented at least monthly until death.
Patients in the PC group who progress will not be allowed to cross over to rigosertib.
All patients in both treatment groups will be allowed, as medically justified, access to RBC
and platelet transfusions and to growth factors (granulocyte colony-stimulating factor
(G-CSF), erythropoietin, and thrombopoietin).